Over the past several years, automated peptide synthesizers have become increasingly valuable in biomedical research as a rapid means by which to produce custom-designed peptides for various uses. Most commonly, synthetic peptides are used as immunogens to obtain anti-peptide antibodies which, in turn, are used either to purify native proteins, localize native proteins, or to inhibit the activities of naturally occurring proteins. In general, when raising antibodies is the object, the peptide of interest must first be conjugated to a carrier protein. Although the reasons for this requirement are not clear, the size of the peptide must be a consideration simply because small peptides often do not meet all the criteria necessary for immunogenicity.
The present inventors have been involved in the production of antibodies directed against synthetic peptides and have found it desirable to expand the strategies of peptide-protein chemistry. The peptide synthesizer offers a means of automating insertion of a reactive moiety at a specific position in a synthetic peptide for the purpose of attachment of the peptide to a reactive group on a carrier protein. The automated synthesis of N-chloroacetyl-derivatized peptides was recently reported for this purpose in Int. J. Peptide Protein Res. 30, by W. Linder and F. A. Robey, pp. 794-800 (1987). The present invention is an extension of this work in which N-bromoacetyl moieties are also added to the amino termini of synthetic peptides by using standard amino acid coupling chemistry. In addition, several methods are described to produce peptide-protein conjugates, peptide polymers and cyclic peptides.